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Are prions truly impossible to destroy?
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- Опубликовано: 12 июл 2024
- Prions are some of the most terrifying biological agents out there. Here is a video detailing (almost) everything I could find about these special proteins.
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A note - I refer to the science of prions as being cool multiple times throughout the video. That's not to say that prion disease is cool, because human suffering isn't cool. But the work that went into figuring out what the prion protein does IS COOL.
Corrections:
1) The ION717 antisense oligonucleotide might not have a mechanism to destroy the prion mRNA, instead just blocking the native prion mRNA from being made into protein by blocking the ribosome. I kind of assumed it would result in the eventual destruction, but the way I worded it was kind of imprecise.
** one more correction - ION717 is not a traditional mRNA - I don't think it actually codes for making a protein - it's function is to bind and disable the body's mRNA for the prion protein - oops!
An antisense RNA/DNA is a sequence of nucleotides that is a complementary copy of another sequence of nucleotides; in this case, ION717 is the complementary strand of the diseased prion mRNA. Hence "antisense" - just like how a "codon" in an mRNA matches with the "anticodon" of a tRNA.
Sense and antisense strands combine to form a double helix, and when mRNA forms into a structure (e.g. a double helix), it basically becomes useless - and useless stuff are eventually broken down by the cell.
@@phylumchannel antisense RNA or siRNA?
An antisense oligo-/polynucleotide is a complementary sequence copy of a given RNA/DNA sequence - in this case, ION717 is the complementary strand of the prion mRNA; it's the same thing as the codon-anticodon relationship between mRNA and tRNA respectively. Sense and antisense strands combine to form a double helix. When mRNA forms into a structure (e.g. a double helix), it basically becomes useless; anything useless eventually gets digested by the cell.
@@phylumchannel Phy! Im back! And I'm so glad you touched at least a little bit about the sickness I was talking with you about, best gift i could get after regaining my freedom.... Love you buddy!
I worked in Hospital, repairing medical equipment.
A room on the ICU floor was suddenly closed off..."DO NOT CROSS" tape, Maintenance installed a lock on the door.
Over the course of a month, they stripped out all the dry-wall and flooring before rebuilding.
We were never told exactly why they went 'scorched earth', but prion disease was everyone's guess.
@@pirobot668beta They do all of that to keep prions away? I thought you only get them from eating something
@@genevievewalsh2007 no chances taken, it's something that cannot be cured nor slowed, nor stopped.
@@genevievewalsh2007 Airborne transmission isn't observed in nature but it's been demonstrated in labs so it's possible. Since the onset is so slow and subtle, any possibility, however slight, demands incredible caution otherwise it could be allowed to spread for decades before detection.
@genevievewalsh2007 the moment you get a prion disease, it's a matter of when, not if, you will die.
@@StephenRWilliams I wish I could go back in time and never read your comment to learn airborne transmission is a possibility :(
What surprised me the most about prion proteins is how relatively rare they are.
Given the sheer probabilistic space there is there are a LOT more possible "metastable" states vs fully stable ones.
The fact that only an handful do lead to this kind of "metastability collapse" is extremely puzzling to me.
Probably is an evolutionary trait, if a biological lineage detects a DNA sequence tends to create metastable forms, it will eventually shut it down, while sequences with really low probability of depeloping a metastable form will be kept via natural selection
I think you got them confused... Prion proteins are the more stable ones. The healthy proteins we actually use are the meta-stable. This is the only commonality in all prions. They are more stable(existing in a lower energy state) than the normal folded protein structure. The currently understood hypothesis in how normal folded proteins transform into prion proteins is even based in that.
@@nicholasfigueiredo3171prions have high thermodynamic entropy, as evidenced by their disordered amorphous structure in bulk.
@@KrashFries yes? English is not my first language but in what way what you said differs from what I said?
@@Koroistro They use to be rare, if you look into it there seems to be a recent jump in the number of people with Prion Disease popping up.
With the prion outbreaks among species of deer in the continental US, I have heard it could take up to 40 years for prions to eventually degrade. The intro mentioning incineration made me wonder if a lack of wildfires correlates to persisting outbreak sites?
That's an interesting hypothesis!
Wildfires do regularly reach temperatures that can incinerate prions, I guess it would depend on how deep into the soil those temperatures go.
Someone ought to look into it
@@bjorntheviking6039 I microwaved a cookie for too long once, I got upset and I looked at the cookie and noticed something awesome. I could see the embers traveling through the inside, I ran the cookie under water and a bunch of steam came out. I have heard root systems act the same, and with how big and spanned they are I imagine those temperatures reach very deep.
The only bad part is that the same phenomena doesn't really happen in human settlements.
I had a brain eating amoeba one, poor fella died of hungry
Oh noes
Took me a little too long to get this😂. Maybe I'm in the same boat as you😅.
greasyRFKjr
My condolences for your loss, sir or madame/in between. I truly hope such a tragedy can be avoided in the future. Perhaps they are in a better place now, beyond the cesspool that is your brain.
(I feel really mean about that last part but i wanted to subvert expectations aaaa-)
OVERUSED JOKE
Honestly the fact Prion disease is so slow acting is scary in of itself. You could have eaten tainted meat years ago and not even know it.
It is actually so slow I wouldn't be surprised if a large outbreak did happen once but everyone involved died of old age or other diseases because the prion wasn't going to act until like way past the average human lifespan of the infected persons so no one ever noticed and because of how prions work, that one community if isolated likely died down entirely without ever knowing the danger they were to the world and sedimentation and other forces probably buried all that dangerous material or it has been scattered so far between samples that the likelihood of a modern human eating that one patch of dirt or grass containing it is borderline ZERO.
@@user-xx7kl7sr6i Dude, learn what a period is
@@user-zn2ub8zs5l you should learn to he nicer.
@@user-zn2ub8zs5l learn to read without them
If anyone is wondering why strong neural connections can be a bad thing, let me pulm out what I learned in neuropsychology: the stronger a neural pathway is, the harder it is to undo or change. As we grow up and learn as children, our brain makes more and more pathways, but as certain stimuli are encountered more often and as some behaviours are repeated, some of those connections strengthen while others weaken or fade away. As we age, we tend to have fewer and stronger connections. And while this allows us to take shortcuts, go on autopilot and so on, it also means that we are less adaptable.
Does too many strong neural connections lead to results like schizophrenia? Sorry if thats a dumb question. Im just a non doctor curious about prion diseases.
@@lucianaromulus1408 no, there’s no correlation and all he is talking about is simply the plasticity of the brain weakening as you get older. Essentially, your brain maintains and promotes axonal pathways between neurons (the connections between neurons) that are being used and therefore there’s this thing called “long term potentiation”, in which neuron signalling becomes quicker and more responsive. A “strong” connection is like knowing how to play piano after years of practise, or eating or even walking. We all have these neuronal and motor pathways in our brain. Schizophrenia is a complex mental illness with a plethora of causes, involving both a combination of genetic and environmental causes, nothing related to those connections.
@memesix5440 isn't Schizophrenia tied to too much Dopamine? I was just wondering if an overly excited connection could contribute to similar outcomes. If not...how is that expressed in a person? He illustrated in the video that too strong of a connection isn't ideal either.
Ahhh, prion diseases. Nature's angry origami. Another awesome video, by the way.
@@HexLabz underrated comment
😂😂😂 aka the deviant folds
Biological analogue to "false vacuum decay"
The Vallabh and Weismann labs recently published a great paper in Science on a tool they developed, called CHARM, that could silence up to 80% of prion gene (PRNP) expression brainwide in mice - this likely surpasses the therapeutic threshold for delaying and even (maybe) reverse symptoms of prion disease. The tool was introduced to mice brains by a viral vector and they even designed the encoded tool to silence its own expression (to reduce off-target effects) after silencing PRNP. More work will need to be done to show how this affects actual developing prion disease and to show minimal off-target effects, but this is a really amazing new approach that has potential to be applied in humans.
@@cjdabes yes, knockout is very effective in blocking disease. However the lack of normal gene function comes with side effects in humans. If the disease is fatal, then side effects are more likely deemed acceptable.
@@kirby145x I agree. We don't know how PRNP silencing affects humans, but murine studies suggest it's a dispensible gene, though some evidence exists for a function in neurons for the native prion protein. Nonetheless, if CHARM-based silencing were ever an approved therapeutic for humans exhibiting prion disease symptoms, I find it hard to believe that those suffering from the disease wouldn't be completely willing to try this modality, given that prion disease is uniformly fatal and has no other therapeutic treatment to reverse symptoms or stave off the progression.
@@kirby145x Well it's sure fatal.
Truly amazing
i live in an area where chronic wasting disease is present in our deer population. we've been told that meat from infected deer is safe to eat, but i've avoided it regardless because potential big scary (i know that there's been some research that shows that it's highly unlikely for cwd to be transmissible from animal to human, but i'm overly cautious). one of the things that skeeves me out about cwd is how contagious it is and that it seems to be able to spread through indirect contact. getting into pure hypotheticals, i've spent many a bored moment thinking about how cwd might present in humans, and even more time spent freaking myself out about the general idea of a prion disease that is contagious between humans in the same way cwd is between deer. definite amygdala pressing there. on the other hand, it seems like the spread of cwd has created strong interest in understanding the disease and how to control it, leading to a lot of new and ongoing research. i know that i'm far from the only one eager to see if the research of cwd offers opportunities to better understand and potentially treat other prion diseases. it would be incredible to find more potential options, like ion717, that could open the doors to treating these diseases
My thoughts exactly. A month ago it randomly occurred to me at work what a nightmare human CWD would be. The fact that common disinfectants like sunlight and boiling things don't touch the stuff gives this a perfect 10\10.
Really hits home in what a fragile state we as humanity all are in. Eggs and single basket and all that. Time to settle space already!
if its gone from cows to humans, I wouldn't be surprised if it could go from deer to humans
@@raffishrabbit hey man, keep it up, you may be proven right but you're preventing yourself from being a *potential* patient. maybe you're being paranoid, maybe you're not, never risk getting any disease especially one as potentially deadly as CWD
Idk, I know nothing about the mechanism how it even spreads. I couldn't find clear info on it. For example, do you have to worry if you know someone who had cwd, in your town, at work, someone who lived in the same building as you or the same room ? I get that it's very persistent in the enviroment, but what does that mean ? I touch a door knob after a sttranger who unknowingly has it and Im done, or I have to feast on an infected brain to have a 50-50 chance ? And what is the load you have to get ? just one misfolded is enough or you need to be exposed to a large chucnk of already accumulated gunk directly to get into danger ? How does it enter, how it gets to the brain ? and what with the sparatic cases, genetical disposition might be enough ? I heard that a significant amount of ppl might be infected (especially in Britain) and this could be an unrevealed reason for many case of elderly dementia. This I know very speculative but scary thought indeed.
Work that amygdala!
phy does a good job on being informative while having a personality at the same time
Thats a lot of work, for a single cell.
Agreed, subbed!
Npc comment 🤡
@@auronxnpc moment lmao
@@jakebrouillette8268 wrong comment section, nobody is gonna pay attention to what a pseudoscientist says, good luck
prions are so interesting and absolutely terrifying to me. like it’s a miniscule nearly impossible chance but technically a protein could randomly misfold at any moment and then you have to watch your own mind deteriorate until you die and theres absolutely nothing you can do about it. i know mad cow disease outbreaks are extremely rare and they do everything they can to watch for and prevent them but i still get a bit paranoid about eating beef. imagine dying in a slow, painful, deeply upsetting way because you got mcdonalds 😭 (sorry, hope this isnt considered trauma dumping or against any of the rules, please feel free to delete if it is)
@@bugfriend24 yes. And its a disease with a higher mortality than rabies.
Bro i fucking love meat but I dont know if i want to meat ever again. Wtf is this bss
Saaaaame
they don't have an infectivity mechanism, they can't evolve to spread because they didn't evolve at all. the misfold has been possible since the first time the protein was ever folded which was probably millions of years ago, it's a fire that can never spread. probably affected one family at a time throughout most of history, like oh did you hear about the Jorgensens, evil spirits got them and their cattle wandered off - and that would be the end of it. industry's ability to distribute it's mistakes is what's terrifying. what you feel for prions I feel for TCDD and BPA and stuff lol.
Hi phy! Thanks for your video, as always :) I'm one of the many people working on software for TEMs, among which is the team responsible for developing next-gen cryo-EM technology (unfortunately cannot give much details on it). It's great to see some practical applications of what the machine will do, and how it can advance science!
Cryo-EM is wild!!
Its the biological version of the Strange Matter apocalypse or false vacuum collapse, where the more stable version simply converts anything around it to this more stable but life incompatible state
And much slower. Not sure if that's better or worse tbh.
The "professional hyperfixator" is accurate, you be at least a little crazy to thrive in scientific research fields :p
Also as a current highschool student with no power to develop anti-prion drugs, I've thought of 2 ways to try and cure prion disease and it's nice to know that I'm not the only one who thought of them and that there are still some people working on a cure! (my ideas were a counter-prion that folds all misfolded proteins into a functional state, and molecular machinery that can un-misfold the proteins)
Cool video, you got a new subscriber!
That's probably a lot better then my absolute hail mary idea of figuring out a way to absolutely mess up and you and the problem-prions, and just hope you don't drop first
Essentially a synthetic nano-machine constructed to only bind to the prion and enzymatically force it back into the proper conformation
Potentially start with chaperone proteins, then alter their structure and target sites to generate the desired effect
🙏🏽 I hope you go to school for molecular Biology or biochemistry and follow through on that curious hypothesis
Potentially possible with AI protein design !
@chupacabra304 the solution doesn't have to be some techno nonsense 😭
This video got teased more than gta6,
worth the wait
idk why but those sad prion faces are so funny.
There is a woman named Sonia Vallabh (she is of Indian descent hence this uncommon family name) who herself has an extremely rare monogenic prion disease that has not gone symptomatic. Despite having no STEM background (Juris Doctor, Harvard Law School), she went to a very unusual way to become a medical researcher and tries to develop a treatment to prevent the onset of symptoms. Her approach is somewhat unconventional: to reduce the amount of normal prion protein in the patient's body as much as possible. I am sceptical of this approach because all we know about the seemly "uselessness" of normal major prion protein come from mice (and you know what a infamous joke of "IN MICE" is in basic research). What if the normal major prion protein does have cruicial biological function in the human body and humans cannot live without it safely? Even if that is not the case, what if there is no safe ways to reduce the amount of it?
Correction:
While Vallabh and her husband did come from the world of law, they DO have a STEM background since they got their PhD's from Harvard in Biological and Biomedical Science.
Also, Vallabh and Weismann just got their recent groundbreaking paper published in Science IM which they developed a compact epigentic editor called CHARM that could be introduced by a viral vector (AAV) and silenced up to 80% of prion gene (PRNP) expression brainwide in mice - this surpasses the threshold for a therapeutically relevant reduction that might delay and even (maybe) reverse the symptoms of prion disease. Truly a cool new tool for scientists at the bench and, perhaps eventually, at bedside, too.
@@cjdabes they didn't have stem backgrounds, they both went back to school after the diagnosis, I believe
@@biggiecheez6879
Going back to school to get a PhD in Biomedical sciences is called gaining a STEM background. I was correcting the original commenter because, as written, they implied that Vallabh and Weismann became medical researchers without any actual STEM background and training - something you cannot realistically do in the modern age of molecular bioscience. They became researchers while acquiring their PhDs and then founded a lab thereafter. I did not omit the fact they changed careers, I clarified their career path.
@@cfromnowhere Okay, but the alternative is dementia and death. Even if the approach doesn't work, it's still testable and a potential solution.
@@biggiecheez6879 having no prior scientific background then? although yeah, I think "getting a PhD later in life as a career change" is enough of a different thing from "no scientific background" to get that separate description
This is a REALLY good video!! I work with other neurodegenerative diseases like Alzheimer's on a molecular scale and the problem is nearly identical (except the fibrils are with a protein called Tau instead).
Love that this video feels like a review paper for a general audience- something sorely needed in science!
That's a perfect way to describe what I'm aiming for! A review paper for the public!
When he said "domain..." My brain went full autocomplete thought "...expansion".
Go back to bed Gojo, your losing it again
@@lancerhades971 Go/Jo
Flopping same my guy
my dumbass also mentally thought "expansion"
Domain expansion
Rapid multiplication prion !
🙏🏽
@@chupacabra304 domain expansion. Imperfect embodiment of replication!
This was INCREDIBLY interesting but I couldn't help but think you sound so much like Saiki's EN voice actor that I just imagined this as being an extra long internal monologue gag from the anime.
I was not ready for Lichen Roxas..
rocksas
Prion diseases are more frightening than rabies because they're a slower, more agonizing death, and it doesn't matter when you discover you have one- you're toast. You can't really "vaccinate" in any way either, even if you think you've been exposed. Whereas rabies has a few treatments with negligible but not zero treatments that may help you survive until it passes if you get diagnosed super early but post vaccination stages. Plus the ability to vaccinate if you think you've been exposed within a certain window. Rabies still scares the ever loving heck out of me though. Like holy crap is it bad.
To me, I think rabies is scarier. The long incubation period for prions means you can still live a full life without ever knowing while rabies symptoms start alot sooner.
@@skeletor2994 rabies can take years, it just usually doesn't. Either way, you're more likely to have an idea that you were exposed to it and there's steps you can take if you act in a timely fashion. Not so much with prions.
11:00 omg i love the fubuki reference. XD didnt expect it at all
Anything that exists can be destroyed. I wholly and completely reject the idea that _anything_ is indestructible or incurable.
@@notsae66 He explained in the first few minutes that infected meat can be incinerated, obviously far beyond the realm of cooking it though
@@j-don5228 Note the "Incurable" part. Destroying the host to kill the infectionnis far from optimal, but I'm sure there _is_ a way to safely destroy this thing.
of course nothing is truly indestructible but things are "practically" indestructible like forever chemicals used in fire retardants or things that dont degrade over a very long period of time.
I recommend you look into the tau protein. It is a functionally unfolded protein in the brain that can form fibrils in a prion-like manner. It is one of the hypothesized causes of Alzheimer. I learned a little about them in uni and from what I remember, they accumulate when their hydrophobic domains cling to eachother, similar to the beta sheet structures you showed in he video. This can be undone by enzymes, but this ability decreases with age. Once a tipping point is reached, they will form the fibrils in Alzheimer's Disease.
Tau tangles are also seen in other neurodegenerative disorders.
3:31 Netherland jumpscare
Legit
@@tommyatomic222 the verstappening just won't leave us alone
This is so engaging and informative at the same time. I love these videos!
I think the thing that scares me is this. There are certanly misfolded prions in our food but we believe they are harmless. But what if they are just mostly harmless.
If everyone that touched lead instantly became stupid we would have known about lead's effects on the brain from antiquity. The fact that it's not fast or dramatic made it hard to realize. By the time we figured out what was going on we had painted our homes with the stuff and were burning in in our gasoline.
The cognitive problems caused by lead were not binary either. We should assume that everyone has had a non-zero cognitive reduction because of environmental contamination.
We may look back and find prions causing small cognitive problems to nearly all humans.
Not only are you making long form educational content, youre also funny asffffff!!. good shit bro!
Watching this like I haven’t read every article about prions I could find
I’m obsessed with them I wish there was more to read about but obviously it’s great that they are so rare lol
They made me consider switching my line of study from chemistry to biology
New drinking game: every time he says the word "incredible," drink.
super cool how prion disease just keeps increasing among cervid populations in my region and hunters just refuse to test
do they just... not care if they eat CWD venison lol? i know theres never been an instance of it infecting a person but we dont know that its impossible (esp in the future when new variations exist) its just not really worth risking
Very high quality video. Informative and entertaining at the same time. Your channel will certainly blow up sooner than later 👍
when you said this was the perfect time to make this video I got a mini heart attack, expecting you to say there was a new prion outbreak somewhere lol
Oh boy! Natural horrors beyond my comprehension! A perfect video for my lunch break.
We love you man so happy it’s finally out I’m gonna put it in my biology class group chat
If prions weren't already discovered, they would be considered too absurd to really exist
PRIONS!!! Love those things (well I don't, prions are terrifying and I don't want anyone or anything to have them, but they are really cool to learn about)
3:23 domain expansion: gene knockout
Ngl, read the title as "Are PRISONS truly impossible to destroy", I was thoroughly confused until you started talking about mad cow disease 🤣
great video. didn't expect sbeve to interrupt an otherwise disturbing topic :P
I misread your name as "phil the neutroPHILE" and thought it was some clever deep layered chemistry joke i couldnt decipher and then realized it said neutroPHIL
it would be great if yeast could be developed as a delivery mechanism for anti-prion strategies. Especially if the yeast that did it was S. Cerevisiae.
I would love to have a doctor yell out GET THIS PATIENT A PINT O' GUINNESS, STAT! That would go a long way toward fostering trust between patient and doctor.
"Guinness is good for you"
"Gives you strength"
-an old guinness advertisement
It's like PFAS but for biology
At this pace I feel like PFAS will be a part of biology too.
Watching this while waiting for my delicious looking cheeseburger is cooling down from the microwave. Wish me luck guys.
Come back in 12 years if your brain is still working!
Cheeseburger out the microwave?
Thank you so much for the video, I have tried to keep up with development around prion diseases, but I learned several new things here. Awesome work, thank you.
Thank you for the tism food
Bone apple teeth
8:46 SBEVE :(
sbren sbeve
Glasses are also cool because they help me see!
Thank you for taking steps to demystify these things!
I think it’s important to note that it has such a long incubation period and such a strange way of spreading, it could just show up and can lay dormant until you’ve reproduced. So people wouldn’t necessarily die out fast enough. So any benefit of it seems to be just accidental
Wow, the timing of this video... I happen to be researching about prions for a group presentation, and was having a lot of trouble getting started because of how little concrete information there was for these proteins. This couldn't have come at a better time, thank you!
I've spent the last 3~4 hours trying to read through a 2008 paper discussing the physiology of the prion protein, and I wanted to share some of my thoughts and takeaways from it (long comment incoming, i'm basically using this to brainstorm somewhere that isn't my group-shared document ;u;)
The paper started off discussing the structure of PrPc, then went into its possible ligands and functions within and beyond the nervous system. There was a lot of speculation, proposals, and contradictory data about what role prions play in motor coordination (hi Doppel), memory, sleep (oh no fatal insomnia), and synaptic activity (yummy Cu2+ ions), but also immune cell development/activation (TCR recruitment? APC maturation?), cell differentiation, apoptosis (triggers it? prevents it?), and a few other body systems and organs (namely neuromuscular junctions, liver, and pituitary) that I ended up skipping because it was no longer related to the topic of our presentation. Then it went into a bunch of signal transduction pathways PrPc may or may not be involved in that I also skipped because by that point my brain wasn't working anymore, and I skipped ahead to the conclusion.
Prions are predominantly expressed in the central nervous system, but in humans they're also found on the surfaces of mature and/or activated lymphocytes and myeloid APCs, along with low levels of expression in other tissues of the body. Prions definitely have a role in the immune system as well as the nervous system, but we don't really know what yet. In the passages leading up to the conclusion, the paper noted that PrPc is sufficiently but not always necessarily involved in a wide range of signal pathways often related to systemic and cellular stressors, but studies conducted on the specifics of these return with contradictory results, and they paint a picture of prions having "seemingly unrelated functions in various cell types."
The paper posited that prions may serve as a "dynamic platform for the assembly of various signalling modules," and that kind of got me thinking. For some reason, prions are a highly conserved feature among animals, most notably mammals but also non-mammals too. They're a key feature of neurons, but also show up in plenty of other unexpected places, yet the role they play in these cells is confusingly subtle, contradictory, and random. Also, maybe this is just me, but the structure of PrPc itself doesn't seem all that impressive to me either? Like, it's just three alpha helices, two antiparallel beta strands, and an unstructured domain filling up the N-terminal half of its ~200 amino acid sequence. I mean, I've never taken a good look at any other protein structure, so I have no basis for the impression I got, but yeah..
This is 100% crack theory speculation now that's completely unbacked by any prior research or knowledge, but I wonder if prions are an evolutionary remnant of animals? They might have been more universally expressed across all tissue systems at one point and played a crucial role in starting signal cascades in response to stimuli, but have since lost that significance as organisms evolved better proteins for more specialized functions. However, since they were so ubiquitous, they still stick around today in unexpected places like in hematopoietic stem cells, leukocytes, and most notably neurons.
TL;DR - I read a 2008 paper and learned that the major prion protein isn't only involved with the central nervous system, but also the immune system and probably elsewhere too, but all data delving into the specifics of that is contradictory and inconclusive. I now have a crack theory that prions used to be really important for signal pathways across many tissue systems, but now only take on subtle roles in the nervous (and immune?) system.
None of this had anything to do with Creutzfeldt-Jakob Disease, which was what my group presentation is specifically supposed to be about, so I decided to drop my rant here :T
The massive unstructured region IS an impressive feature! Flexibility can allow you to interact with a wider variety of stuff. Might be worth seeing the list of things the prion protein binds with!
@@phylumchannel Oh, that's true! I forget that there only exists models of the structured domain, leaving out an entire half of the prion protein. Definitely something I should look into more :p
I love detailed talks about proteins and prions, Thanks for the thorough and informative Video as always 😎
i always considered misfolded prions as a new "ground state" in terms of the energy levels. Pretty much they are highly stable because they are in an energy "trough" and you must add additional energy to break them down.
I've been waiting for this for so long
I mean, if I had a prion disease, I'd take the risk of my prions becoming drug resistant over the certainty it will get worse.
Wow, functional prions!!! That's incredible!!!
Amazing videos dude. Your well on your way to becoming a huge name in the science space 😊
YES, the ubiquity of solid knowledge available on RUclips is mind blowing ❤
Glasses are very versatile.
I have been aware of and afraid of prions for quite some time, and I did not know about the hidden gene. Very nice video!
I remember when the Mad Cow disease was all over the news in the 90s.
this is why I never eat other people's brains
Jeez, imagine if something like rabies was a prion disease? That's the ultimate nightmare disease!
i used to be scared of prions. i didn't know i had prions in me already. thank you for sharing all this interesting information. i don't want to have prions
loved the experience as a first time viewer, but as a biology student the bit about evolution eliminating a useless & potentially harmful gene made me actually gasp and skip back to see if I'd misheard. Bestie NO. Even putting aside the assumption that an average animal's DNA isn't overwhelmingly junk and leftovers, prion diseases are not common enough by far to be under much selection pressure. Even more importantly, as far as I know most of them would never even be subject to selection pressure as their symptoms are delayed enough that most organisms affected would have offspring before being killed by prion disease. Thank you for coming to my TED talk
I'm not a nerd or anything I mean I'm 16 but this is super cool and informative and entertaining
1:23 Ah yes, how could you resist from making 2 gaming references at once 😂
9:10 Ah yes, rookie mistake is assembler code, but it's DNA 😂
Read about vCJD and UK in the early 2000s. Scary shit, especially how some of the patients deteriorated
Baffles me that protien origami is a vital role for our body
I read a book once about a space generational ship arriving at a planet which was compatible with human life. Except it wasn't...prions. The ship had to leave the planet.
I wonder if the existence of the prion doppelganger is related to why the brain is so sensitive to prion missfolding to begin with
Are the correctly folded prions even called prions? I thought they were just called proteins
the name of the protein is "the major prion protein" - PrP(C). The diseased form is PrP(SC). They are both technically the prion protein, and we have methods to distinguish the two.
"Prion" can also refer to a whole bunch of other proteins that share the characteristics of the major prion protein, so the term "prion" is absolutely kind of confusing.
My guess is that prions ("diseased" proteins) are named after the "Prion" (nerve cell membrane protein)?
@@Gelatinocyte2
Stan Pruisner gave the names to prions as "protinaceous infectious particles", and the term "prion" for short, in his 1982 paper originally describing this new biological principle of disease. He also specified the pronunciation as "pree-on", so as to distinguish it from the type of bird know as a prion (pronounced "pry-on").
There is a encoding the prion prorein called PRNP, the name is which is derived from the original prion description. The gene has some normal function in cells, possibly in a neuronal patgway, though this function is somewhat obscure. Nonetheless, mice with the PRNP gene knockout seem to basically be okay or unaffected.
It's basically grey goo but on a cellular level (and it actually exists, it's not just a scifi concept)
Finding out these things can evolve is nothing short of terrifying. And I don't normally find biological stuff terrifying.
This video scratches exactly the itch for Cool Biology Shit that is frequently unscratched since dropping my biology major. If someone can IV drip organic chemistry expertise directly into my veins I might go back and get it someday 😂
:O! Lichens!! Prion destroying enzymes!! omg... man, I don't wanna be too optimistic but that is so cool! Man... if we could cure chronic wasting disease with lichen somehow, it would maybe be cool for reindeer, if they could think of it that way. Like, in that scene from frozen two where the reindeer talk, haha. "A part of my diet is curing my this scary disease? Awesome." They would maybe think. (Of course, I don't know if the lichens that produce the enzymes that reduce misfolded prion aggregate are the same kinds of lichen that reindeer eat, but maybe they would think it was cool anyway?)
Cautious optimistic is perfect!
the image of the mad cow disease fire pits are firmly lodged in my brain from childhood. the horror still has a dark corner of my brain all to it's self.
I wonder if Prions are vulnerable to getting chemically reacted in the environment. Prions always seems to be creature to creature but not environment to creature.
There is a hereditary form of prion disease and that notion absolutely terrifies me. You can go years and years without even knowing and then you die in less than a year once symptoms start. Thankfully it is fairly rare, but if one of your parents has it you have an over 90% chance of inheriting it. Anyway, thank you for the video.
Both sporadic and generic CJD is extremely rare.
0:36 there is a theory that it’s your brain subconsciously wanting to constantly keep its fear response sharp, so instead of releasing just a normal amount of primordial curiosity, it releases more than a water dam can ever hold
Of course this is mostly overly exaggerated, only the first sentence is true
studying histopathology which just saw amyloid stained slides a couple of weeks ago, i cannot imagine what would brain tissue loaded with prion look like, already seen the scary signs of metastatic cancer and that is already confising for me to figure what the tissue is supposed to be
Former anatomist here; I was always terrified of doing brain recoveries or anything that would require us to open up the skull. Not to mention, the countless times we'd have to sever the spine with our scalpels. Cutting myself was my biggest fear of all. Fortunately, I never did, but a few of my coworkers had sharps incidents.
Never been here before.
00:18 into the video & subbed.
Teach me.
I hate that you have so few viewers
I thought ingesting prion will make me stronger, but then I remember overexcited neurons may cause seizures.
English is not my first language and I'm still learning but I understood, like, 80% of the video. Great job!
Isn't it the case that stomach acid will still manage to break down some amount of the prion aggregate? It is at the end of the day made of the same 20 protein blocks that all biological systems are familiar with. Plastic I can understand, especially with how acid resistant it is, but I would think that the aggregate would get degraded enough by the entirety of the food chain to counteract the small quantity of creatures producing it
A NEW VIDEO LETS GO!
I am quite surprised that nobody has tried to make an armor(figuratively) out of prions given how strong their beta sheets are
I sure do miss all the horse meat, can't get it now-a-days though, used to be everywhere and in everything feels like.
Have computational groups looked at predicted structures for the misfolded prions?
@@forwhomthetacobelltolls9789 I want to be smart like you, where should I start?
The biological version of Animal Crossing's duplicating paper airplane. Terrifying...
Thank you! Finding great content when you randomly wake up at 330am is tough. Yah did good kid. 👍 😂😅
prions are like a zombie apocalypse on a celular level
i think we seek fear for a similar reason why animals eat live food
Even if that drug that's in trial was successful how would we eliminate prion diseases in animals like Chronic Wasting Disease? If it's left unchecked it could totally eliminate wild deer, elk, moose, etc, in North America
ALMOST!??! What are you hiding 🤔
I was hoping for sbeve.